The purpose of this project is to study the mechanism by which gastrin, histamine and acetylcholine stimulate gastric secretion. These studies will utilize purified oxyntic cells, parietal cells and chief cells. We will attempt to determine if gastrin, histamine and acetylcholine stimulate oxygen uptake, glycogenolysis and pepsinogen secretion by mechanisms which involve cAMP, cGMP and phosphorylation of soluble and membrane proteins by cAMP-dependent and cAMP-independent protein kinases. We will attempt to determine if gastrin, histamine and acetylcholine interact directly with the secretory cell or with some other cell type and to clarify the interactions between these stimulators of gastric secretion. Because of the central role of cAMP-dependent protein kinases in hormone actions and their probable role in gastric secretion, the cAMP-dependent protein kinase will be studied in greater detail, especially with respect to the nature of the interactions between the catalytic and regulatory subunits.